Nature or Nurture? Role of the Bone Marrow Microenvironment in the Genesis and Maintenance of Myelodysplastic Syndromes

SIMPLE SUMMARY: Myelodysplastic syndromes (MDS) like many other blood cancers is a disease of the bone marrow, in which the spongy part of the bone is not able to produce enough healthy blood cells. MDS is primarily a disease of the elderly, but it can affect people at a younger age as well. The disease arises as a result of a combination of complex processes that is thought to be primarily driven by accumulation of genetic mutations in the stem cells. However, there is an increasing evidence implicating the bone marrow environment as a fertile milieu where these mutated stem cells thrive and give rise to the disease. In this review, we have discussed the role of blood stem cells and how other cell types in the bone marrow environment interact with each other, therefore contributing to MDS. In addition, we discuss the therapeutic strategies that can be exploited to treat MDS. ABSTRACT: Myelodysplastic syndrome (MDS) are clonal haematopoietic stem cell (HSC) disorders driven by a complex combination(s) of changes within the genome that result in heterogeneity in both clinical phenotype and disease outcomes. MDS is among the most common of the haematological cancers and its incidence markedly increases with age. Currently available treatments have limited success, with <5% of patients undergoing allogeneic HSC transplantation, a procedure that offers the only possible cure. Critical contributions of the bone marrow microenvironment to the MDS have recently been investigated. Although the better understanding of the underlying biology, particularly genetics of haematopoietic stem cells, has led to better disease and risk classification; however, the role that the bone marrow microenvironment plays in the development of MDS remains largely unclear. This review provides a comprehensive overview of the latest developments in understanding the aetiology of MDS, particularly focussing on understanding how HSCs and the surrounding immune/non-immune bone marrow niche interacts together.